O-Cresol → HCID 13039294, compound

To a mixture of 6.23 g of trans-1-ethoxycarbonyl-3-phenyl-4-piperidinol, 7.21 g of triphenylphosphine, 2.97 g of o-cresol and 250 ml of anhydrous benzene is added, dropwise at 5° C. under nitrogen over a 90 minute period, a solution of 4.79 g of diethyl azodicarboxylate in 250 ml of benzene. After the addition is complete the mixture is stirred overnight at room temperature. The solid is then filtered and washed with benzene and the filtrate concentrated in vacuo to an oil. The oil is triturated overnight in a stoppered flask with 250 ml of hexane. The hexane is decanted and the gummy solid is triturated with more hexane and the hexane solution is filtered. The hexane filtrate is washed with 10% aqueous sodium hydroxide solution (3×75 ml), 2 N hydrochloric acid (100 ml), water (100 ml), saturated sodium chloride solution (100 ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to a yellow gum. The gummy solid previously obtained is washed with ether. The ether filtrate is concentrated in vacuo and the residue is partitioned between 150 ml of hexane and 50 ml of 10% sodium hydroxide solution. The phases are separated. The hexane phase is washed with 10% sodium hydroxide solution, followed by 2 N hydrochloric acid solution (50 ml), water (100 ml), saturated sodium chloride solution (100 ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting gum is combined with the previously obtained gum. Trituration of the gum with a 2:1 mixture of petroleum ether:ether affords a colorless solid. A second crop is obtained from the filtrate. Filtration through a silica gel plug using dichloromethane as solvent, followed by trituration with 2:1 /petroleum ether:ether solution and filtration affords product as a colorless solid, mp 119.5°-121° C.

1. additionis added, dropwise at 5° C. under nitrogen over a 90 minute period
2. additionAfter the addition
3. filtrationThe solid is then filtered
4. washwashed with benzene
5. concentrationthe filtrate concentrated in vacuo to an oil
6. customThe oil is triturated overnight in a stoppered flask with 250 ml of hexane
7. customThe hexane is decanted
8. customthe gummy solid is triturated with more hexane
9. filtrationthe hexane solution is filtered
10. washThe hexane filtrate is washed with 10% aqueous sodium hydroxide solution (3×75 ml), 2 N hydrochloric acid (100 ml), water (100 ml), saturated sodium chloride solution (100 ml)
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo to a yellow gum
14. customThe gummy solid previously obtained
15. washis washed with ether
16. concentrationThe ether filtrate is concentrated in vacuo
17. customthe residue is partitioned between 150 ml of hexane and 50 ml of 10% sodium hydroxide solution
18. customThe phases are separated
19. washThe hexane phase is washed with 10% sodium hydroxide solution
20. dry with materialdried over anhydrous sodium sulfate
21. filtrationfiltered
22. concentrationconcentrated in vacuo
23. additionTrituration of the gum with a 2:1 mixture of petroleum ether
24. customether affords a colorless solid
25. customA second crop is obtained from the filtrate
26. filtrationFiltration through a silica gel plug
27. filtrationether solution and filtration
28. customaffords product as a colorless solid, mp 119.5°-121° C.

ORD record

ord-5086bafeba574d1e9acffc221bdb5f73

Source dataset

uspto-grants-1983_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04382141